9H49

Crystal structure of the adduct between human serum transferrin (apo-form) and cisplatin

Summary for 9H49

• Entry DOI: 10.2210/pdb9h49/pdb
• Descriptor: Serotransferrin, CITRIC ACID, PLATINUM (II) ION, ... (5 entities in total)
• Functional Keywords: cisplatin, metallodrug, anticancer, metal complex, methionine/cisplatin adduct, metal transport
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 152638.26

Authors

Troisi, R.,Galardo, F.,Ferraro, G.,Sica, F.,Merlino, A. (deposition date: 2024-10-17, release date: 2025-01-22, Last modification date: 2025-01-29)

Primary citation

Troisi, R.,Galardo, F.,Ferraro, G.,Lucignano, R.,Picone, D.,Marano, A.,Trifuoggi, M.,Sica, F.,Merlino, A.
Cisplatin/Apo-Transferrin Adduct: X-ray Structure and Binding to the Transferrin Receptor 1.
Inorg.Chem., 64:761-765, 2025

PubMed Abstract: Here, we report the X-ray structure of the adduct formed upon reaction of cisplatin, one of the most prescribed anticancer agents for the clinic treatment of solid tumors, with the apo-form of human serum transferrin (hTF). Two Pt binding sites were identified in both molecules of the adduct present in the crystal asymmetric unit: Pt binds close to the side chains of Met256 and Met499 at the N- and C-lobe, respectively. In the crystal structure, the cisplatin moiety bound to Met256 also interacts with Ser616 from a symmetry related molecule. Structural analyses, together with in solution data, demonstrate that the presence of iron does not affect the ability of hTF to bind cisplatin and that the cisplatin binding does not significantly alter the overall conformation of the different forms of the protein that remain able to form a complex with the transferrin receptor 1 (TfR1). These data suggest that the different hTF forms can be used as nanocarriers for targeted (combined) metallodrug delivery.

PubMed: 39711171
DOI: 10.1021/acs.inorgchem.4c04435

Experimental method

X-RAY DIFFRACTION (3.52 Å)